All right. Hello, everyone. I'm Tara Bancroft. I'm one of the Senior B iotech Analysts here at TD Cowen. I want to thank you for coming to TD Cowen's 46th Annual Healthcare Conference. Our next session is a presentation and Q&A with Whitehawk Therapeutics. From Whitehawk, we have Dave Lennon, the CEO. Thank you so much for joining us. We're really looking forward to your presentation and the Q&A. Without further ado, I'll just let you kick it off.
Great. Well, thanks, Tara, and thanks for Cowen for having us here in Boston today. Next year, a little warmer, please. I'd like to introduce Whitehawk. We are advancing a differentiated portfolio of next-generation antibody-drug conjugates, or ADCs, that target a broad array of cancer indications. As a company, we've made tremendous progress since we launched last year. Actually, we've moved and progressed now two assets into the clinic, HWK-007, an ADC, that targets the broadly expressed tumor target PTK7, and HWK-016, an ADC targeting the highly expressed tumor target in gynecological cancers, MUC16. I'm excited about this acceleration of our pipeline and eager to talk to you today about why I believe Whitehawk will continue to separate from the flock of ADC competition. There's more of that if you like that one.
The reminder that statements made on today's presentation will include forward-looking statements representing our views as of today, only. Whitehawk was founded on three cornerstones, differentiated science, proven leadership, and an execution-focused mindset. We began by in-licensing a three-asset ADC portfolio that we believe positions us to unlock high-potential ADC targets that are clinically validated, yet not yet inundating, meaning that we still have the opportunity to be first in class, if not best in class. By leveraging clinical validation from prior generations of ADCs, we know we have druggable tumor targets, and because these targets, we develop are broadly overexpressed, we can apply them in high-potential cancer indications with significant patient populations and unmet needs.
We believe our targets, PTK7, MUC16, and the third target, SEZ6, are highly compelling for their tumor-specific expression and limited normal tissue distribution, offering the potential to be selective in tumor killing with reduced toxicity based on our platform. We think the next generation of ADCs will be born from a marriage of these kind of validated targets with differentiated and optimally engineered linker payload technology. That's why underlying each of these programs is an advanced ADC technology platform, an ADC architecture that is based on a novel topoisomerase I inhibitor, and a highly stable next-generation linker payload chemistry designed to improve the therapeutic index of our ADCs. I'll get into that in more details in a moment. That's the scientific background of the company.
Equally important is having the right team to carry it forward, Whitehawk is led by a management team and board both comprised of leaders with deep ADC experience and a track record that reflects operational excellence and M&A success. Finally, as a boldly pragmatic organization, we're lean, focused, and execution-minded. Capital efficiency is a core part of our DNA. We ended Q3 2025, our last recorded statement of financials, with over $160 million in cash, which gives us runway into 2028 and enables us to report on anticipated clinical milestones on all three of our programs before that point. Let's dig deeper into the science that is behind our next-generation ADC architecture. Again, it's really engineered for selective tumor delivery.
It is we couple that with bioconjugation, which leads to modality-leading stability. Ultimately, we have optimized a TOPO1 inhibition for maximal tumor killing while minimizing potential toxicity. We believe there are many ADC companies out there that say they are differentiated. Let me really highlight what makes our program truly distinct. First, in tumor targeting and effective antibody design, we utilize high-affinity antibodies that provide precise tumor recognition and sustained target engagement tailored to each of the targets that I described earlier. We benchmark all of our antibodies against reference monoclonals from prior and current ADC programs to ensure that we have best-in-class target engagement.
Importantly, our antibodies have been engineered with an attenuated Fc region, which is recognized, which we recognized early on, I should say, and now the field is starting to recognize more and more, is critical to minimize undesired immune-mediated ADC uptake, particularly as in lung-resident macrophages, where it can potentially cause lung damage and lead to interstitial lung disease, a key toxicity associated with topo one ADCs. Building off our advanced targeting approach, we have spent a lot of time on the often-overlooked step of ADC construction, which is bioconjugation or how linker-payload structures are actually attached to the antibody. This is where Whitehawk chemistry really stands apart. The field has seen value in moving to ADCs that utilize a new class of topoisomerase inhibitors as payload.
Interestingly, we estimate more than 95% of new TOP1 ADCs in clinical development today still use an older bioconjugation approach defined by single-chain partial site-specific bioconjugation. In this process, the bonds normally hold antibody heavy and light chains together are broken, and single-chain linker payloads are added into those broken sites, blocking the typical reinforcing stability that the natural interchain bonds provide. This process introduces inherent instability in the ADC construct. By removing these normal disulfide bridges between antibody chains, you compromise structural integrity of a antibody as a whole. Additionally, once in circulation, these single-chain linker payload attachments become vulnerable to attack and cleavage, which leads to premature release of free payload into circulation, payload that is no longer targeting the tumor and can circulate and damage normal tissue.
In essence, the standard process used by competitors is fragile, prone to free payload release, and may lead to high rates of class payload toxicities. In the topo class, that's often hematological in nature. The Whitehawk approach is truly unique when it comes to bioconjugation. We add linker payloads to the monoclonal antibody at carbon-bonded pairs, shown here as dual payloads, as the stars inked together with the green chains. This strategy effectively re-bridges native monoclonal antibody chains, replacing the disulfide bond with a new carbon bridge in the linker. This carbon-bridge cysteine re-pairing method restores the antibody's more natural state, enhancing the overall stability of the ADC compared with what is achieved by traditional single-chain bioconjugation.
Building on that, we employ an additional bioconjugation step, linker hydrolysis, to lock the carbon-bridge structure of the ADC, further improving stability, reducing free payload release, and limiting potential payload toxicity. We go through this in detail 'cause it's really important to understand the fundamental differentiation that we, as Whitehawk, deliver to the marketplace that is crowded with other ADCs. The third Whitehawk differentiator is the tumor-busting business end of our ADCs. We do a number of modifications to this portion to improve half-life and overall deliver a highly potent tumor payload. We use proprietary modified exatecan payload that is different from a lot of our competitors who today are using pure exatecan.
Pure exatecan, while extremely potent in its TOP1 inhibition, can often target the bone marrow where it is retained, leading to significant hematological toxicity, particularly as measured by grade III neutropenia. In contrast, our modified version retains potency but with less toxicity, particularly in regards to this impact in the hematological space, and we believe this heme-sparing profile will help address the challenges like severe neutropenia that have emerged with exatecan and exatecan-like payloads found in most competitor ADCs. Taken together, these elements represent an elegant and cohesive engineering solution designed to deliver best-in-class stability, safety, and tumor potency, key components necessary to deliver on the promise of next-generation ADCs. Now to reiterate, all TOP1-based inhibitors or platforms are not created equal. Let's take a look at how our platform stacks up against our peers.
When you look at the average TOP1 ADC platform on the right, we think about three key parameters of non-clinical evaluation that are really important. What's tumor potency in xenograft studies? What's the ADC stability in circulation? What's the overall safety as measured by the highest non-severely toxic dose in GLP monkey studies? Based on this, you can see that the Whitehawk platform offers a much higher degree of stability, 5-25 times more stable in circulation, and this contributes to a 3-10x improvement in potency and a 2-3x higher safety margin in non-primate studies. Overall, a demonstration of the improved therapeutic index that we can achieve with the Whitehawk ADC platform. We're applying this platform to three different targets.
It's the same construct that's utilized, same linker-payload constructs that's utilized in each. We're rapidly advancing each of these programs into the clinic. As I mentioned, HWK-007 and HWK-016 are already recruiting patients in a phase I dose escalation portion of their study. And we look to have data on these programs in the first half of 2027 after we've accumulated sufficient number of patients to really demonstrate the potential of this profile. Ultimately, our third program, SEZ6 , will follow closely behind the first two, and we expect to start phase I in Q3 of 2026. That's the overall story for Whitehawk. As I mentioned, a differentiated ADC platform with three really promising shots on goal that are coming in the clinic currently.
As I mentioned, previously, each of these has the opportunity in multiple cancer indications. I would just point out that HWK-007 is probably the most broadly expressed tumor target that's yet to be exploited in the marketplace. Initially, we're focusing on non-small cell ovarian and endometrial cancer, but with expansion potential into breast, GI, prostate, and head and neck cancer, with significant potential to treat a number of different cancer indications with that program. Our HWK-016 program is more focused in the gynecological space. MUC16 is a super expresser in this space, and there's some really interesting parameters. It's a very well-known tumor target amongst gynecological oncologists, because it's cleaved into the circulating biomarker CA-125, which is often a measurement of tumor progression.
Through clever design of our targeting approach in this molecule, we think we have a best-in-class treatment for ovarian and gynecological cancer with this program. There are also expansion potential here into some novel tumor targets that are not being targeted well by ADCs today, is like mesothelioma and pancreatic cancer. SEZ6 is actually a neuroendocrine tumor that is often expressed in small cell and neuroendocrine, other neuroendocrine neoplasias, as well as some CNS tumors. Here, as with each of these programs, there have been precedent molecules that had demonstrated initial efficacy signal, so we know that these are targetable tumor markers. That's a view of Whitehawk and our platform, the progress we've made over the last year.
We're really proud of the opportunity that we have here to deliver a differentiated set of ADCs to patients in the very short term. With that, I'll conclude my prepared remarks and we can go to questions.
All right. Sounds great. Maybe we can come sit over here.
Sounds great.
All right. Thanks for that presentation, by the way. It's always good to get an overview. I guess, Dave, I'll ask you, we'll start on PTK7.
Mm-hmm.
You know, that one is the furthest along and as we think about upcoming data, what kind of proof points are you focused most on in this first in-human study? Is it, you know, what's the highest priority? Is it safety? you know, the therapeutic window, PK, stability, you know, in that data?
Right.
especially how should we think about that in relation to historical PTK7s?
Mm-hmm
...and the issues that have been seen there?
Yeah. Most of what we know about PTK7 as an ADC target comes from Pfizer's Cofetuzumab pelidotin program. It was Pfizer-AbbVie collaboration. Demonstrated some initial safety signals in non-small cell and ovarian cancer. We're building off of that precedent data as we go after this target. We have both of those indications in our initial clinical trials, and what we'd be looking for with our dose escalation is first that we can clear sufficient number of doses to get into the efficacious range, of course, while limiting any DLTs, which, you know, in this class are often driven by hematological toxicities that I mentioned.
We'll be looking out for those, looking out for those rates even at grade lower than DLT to see are we proving forward the hypothesis that we can be a safer product overall. That should allow us to dose to levels that drive the potential for greater efficacy with this program relative to, you know, the initial data that was seen with the Pfizer program. Ultimately, things like PK, and stability are proof points that demonstrate if we achieve the efficacy and safety we wanna see, but aren't probably inherent for us in this initial phase. We've constructed these ADCs to have sufficiently long half-life for Q3-week dosing, and we feel really confident in our ability to dose patients effectively that way.
Okay. How about maybe set up some comparisons for us? 'Cause there.
Sure
...other PTK7 ADCs that are currently in the clinic now-
Mm-hmm
...and some that we'll even see data from this year as well.
Yep.
You know, maybe you could talk about the different... The importance of your payload?
Sure.
Let's keep it focused on you.
Yeah
How that could compare to other data sets that we see this year?
Yeah. Thank you for taking me off the hook for talking about my competition. What I will say is a couple things. I think first a lot of these programs are kind of starting around the same time. You know, we'll get maybe data from one of the first ones. There'll be a bunch of us following with kind of looking for improvements. I think what's really key to mention is to come back to the payload itself. When you think about TOP1 inhibition, there's really two classes of payloads that are really emerging. One is exatecan and exatecan-like payloads. I would say deruxtecan and deruxtecan-like payloads. Generally, when you have exatecan payloads, they're more potent, but they're more toxic.
When you have DXd-like payloads, they're less potent, but also less toxic. The challenge for your linker system is how can you modify kind of the performance of either one of those payloads to, you know, keep potency while managing safety or improve potency while keeping the safety. That's kind of the trick of what you're trying to do. Our approach relative to our competition in the PTK7 side really focuses from a deruxtecan-based or from a deruxtecan-like structure, which should allow us to deliver better safety for sure. The question is: Can we generate the dose and the potency required to deliver similar or better efficacy to an exatecan payload? I think that's where you'll see the difference.
I can almost guarantee that almost any exatecan payload is going to generate 25%-40% Grade III neutropenia. That's something that we should avoid in our platform, and that's where we think, the real advantage will be, not necessarily just in that initial late-line monotherapy setting, but more importantly, when you think about combinations and moving into earlier lines of therapy, having a cleaner safety profile to combine with chemos, with IOs, with TCEs, will be important to the long-term value, that our platform can provide.
Well, speaking of longer term, you also mentioned, some potential indication expansions.
Mm-hmm
...even beyond the ones that you're looking at now.
Yep.
I think you mentioned breast, GI, head and neck. What would you want to see to prioritize any or all of those?
Well, I think the first order in the very competitive ADC world, not just on our target PTK7, but against other targets that are out there in the TOP1 class, we really want to see a best-in-class profile. We really anchor our readouts to say, if we're not gonna be best in class, then we shouldn't be expanding the programs, because others will get there eventually if they are better. What we're really looking for in that first phase is a demonstration of best-in-class efficacy, which in the non-small cell space starts with an ORR of 35%-40%, you know, roughly five and a half- six months of PFS. In the gynecological space, it's 50% ORR and greater than six months PFS.
Those are the benchmarks we have in our internal decision-making, have established to move forward. Importantly, to move forward in other indications, you have to look at, you know, what are other ADCs showing within that space, what combinations are important, and that'll be a selection process we'll go through as we accumulate more data and understand kind of what we can do with our PTK7.
Okay, great. I wanna dig a little bit more into your discussion on safety.
Mm-hmm.
When we do see the data and as you think about it for you guys leading up to that, what are any particular safety events that you're especially looking out for and you want to see at a certain level? just which one?
TOP1 safety is defined by hematological toxicity, you're kind of looking for that. Obviously the most severe cases, grade 3, grade 4 hematological toxicity, even grade 5 sometimes when you think about febrile neutropenia, that's something you're looking to avoid at the extreme end. Even in the earlier stages, grade 1, 2 % and absolute values will be things that will be indicative of where we're going with the profile overall and be important to establish. The second thing is we wanna see is really a clean ILD profile, pneumonitis profile. I think that we have come to really believe that attenuation of the Fc region of an ADC can really bring down ILD rates sometimes to zero, that that is not always done with programs.
Certainly in the non-small cell space, it's been really problematic for programs. We saw with I-DXd recently, for example, clinical hold, it was released, good thing, but it can be problematic, and it's particularly often augmented when you think about using ADCs in combination with IO, where you get sometimes doubling of ILD rates when you add IO into the mix. That's something we second kind of component we wanna evaluate and look at. The third thing for PTK7, there was potentially on target toxicity related to headaches that was seen with the Cofetuzumab program, and that's something we'll be looking out for.
It's a inflammatory type headache that's treatable with corticosteroids, but I think in all transparency, we wanna make sure we're kind of staying on top of that, as a potential issue.
Okay, that makes sense. All right, I think we should move on to MUC16.
Sure.
Now your second-
Yeah
... clinical paroling in that. How should we think about how it compares to the approach that you're taking with PTK7 in terms of enrollment speed, the speed at which you increase the dosage for each of the cohorts-
Yeah
... how many dose cohorts you wanna treat before showing data, things like that?
We're really excited about MUC16 because it is this kind of super expressor in gynecological cancers. three- 10 times, sometimes more highly expressed than FR-alpha, NaPi2b, B7H4, CDH, Claudin-6, CDH6. There's really a great starting point with our HWK-016 program of this super highly expressed tumor target. The issue has been that, you know, it gets cleaved and circulates in the blood, and if you target that portion of the molecule, you can't actually get to MUC16. A very clever targeting approach which bypasses that circulating CA-125 by targeting the membrane retained portion of MUC16.
Now that we think is really exciting, has been really exciting when we've talked to Gyn-onc KOLs who, you know, really know this target extremely well and investigators who know this target extremely well and really want therapies that can go after this target. They're really excited about that. We think this study will recruit really quickly because of that and because of its focus in ovarian and endometrial cancer. We really think it has potential to be best in class based on that tumor-targeted approach, or the target itself, but also, you know, in combination with our technology. Now, when we start our clinical trials, you know, we look at, well, where do we think the efficacious dose range is going to be?
What we've typically seen is that we are active in non, in xenograft studies around 1 mg per kg, in generating regressions within those studies. That, what we've seen is typically translates directly into a dose you need in human studies. What I can say, I'm not gonna say what doses and dose cohorts just yet, but what I can say is we're starting above what we think is the minimally effective range, and that we should be able to escalate quickly into a very efficacious range of the molecule, which will allow us to test and have an understanding of whether or not we're seeing responses quite early in this program.
Okay, great. Maybe some context in the treatment paradigm, you know, with other antibody-based therapies, you know, how broad do you think this can be used, you know, in terms of genetic expression?
Mm-hmm.
There's ELAHERE, you know.
Yeah
... endometrial doesn't have a whole lot.
Well, I mean.
Where do you see this fitting in?
Yeah, I mean, MUC16 is one of these targets that, as I mentioned, super expressor, but it means almost everybody expresses it in ovarian cancer. Even the lowest expressing MUC16 patient is a high expressing FR-alpha patient. From a kind of absolute expression level, and they are not terribly correlated as biomarkers. Low FR-alpha expressing patients are still quite high in their MUC16 expression. We allow patients who have had, you know, of either status into the trial. They just have to have had standard of care, and certainly will evaluate what it looks like, you know, post ADC utilization on the MMAE based payload that Mirv has in the trial itself.
Okay. Maybe you know, I know you went into some detail on the SEZ6.
Mm-hmm
... and that will be the third clinical candidate before the end of the year. Maybe a little bit more on the first part, what else do you need to do to actually get to the first patient dosed? Then maybe just kind of some comparing and contrasting between this program?
Sure
... the other programs. Like what are the different types of risk rewards that you see for this?
Yeah. You know, the third program is, you know, is a little further behind when we licensed it. Part of the development has been around the fact that it's a biparotopic antibody, so it binds to two different portions on the SEZ6 molecule. That actually has been shown, we've demonstrated now, that improves internalization and leads to greater potency of the targeting approach itself, at least in non-clinical studies. The development of the bioconjugation approach for a biparotopic molecule is slightly different than a monotopic or monoclonal antibody, just because of the nature that the heavy chains are different between, and the light chains are different between each molecule. That leads to some differences that have...
we've been working very quickly to kind of assemble, but it leads to a slightly different approach than we've used for the first ADCs. We have tuned that all now to be as effective as anything we've seen within that context. We've demonstrated that our antibody approach is more potent than other SEZ6 competitors in the space, and that the platform is as effective as our parent molecules with this on a biparotopic antibody. That we think is a really promising kind of best-in-class molecule in what is becoming a more crowded small cell and neuroendocrine space with DLL3 and B7H3-based targets, as well as SEZ6. Like we said with MUC16, SEZ6 is still the highest expressing target within those neuroendocrine origin tumors, and we think a great starting point, again, for launching a best-in-class molecule.
Okay. I guess with the last few minutes, it would be helpful to hear more about how you're thinking about strategic prioritization.
Mm-hmm
... balancing capital allocation by program, and like what we can expect there for OpEx and in that your appetite for partnerships?
Yeah. We get this question a lot, I think often because people don't always believe we can run three programs in parallel on our cash burn. We are incredibly capital efficient. We started the company with the goal to have sufficient capital get to clinical data on all three programs. We continue to be able to execute on that. We've executed exactly to plan, if not ahead, from a time perspective, but also from a cash burn perspective. We burn roughly $15 million-$17 million a quarter. That takes us with our current cash position into early 2028. You know, our goal is to generate sufficient data to make a determination of what's the value of each of the assets. Be able to then independently articulate the investment case for each of them.
I think about prioritization only in the context of understanding what we have in terms of next data. Right now, you can make some assumptions, but I think it's gonna be driven by what we actually see within the data. Is PTK7 the best-in-class PTK7? It makes a lot of sense to put a lot of investment into PTK7 because you have a lot of opportunity space there. Is MUC16, you know, the best-in-class ovarian cancer drug? Sure, but it's not as expansive as PTK7. There are obviously trade-offs down the road. Also hopeful that, if each of these are best in class, they make their own case.
All right. Great. Maybe I'll end on this question, which I always think is interesting to ask. What do you think is the most underappreciated aspect of Whitehawk?
You know, I think the fact that we have three clinical shots on goal in parallel as a early-stage ADC company is vastly underappreciated, in the context of many companies who have, like, one shot on goal and what that can turn into. I think there's really opportunity for kind of massive value inflection based on that, as we move forward, and that's the, what I hope investors come to appreciate.
Okay. Great. Well, thank you so much, Dave.
Thank you.
... for your time and for being here, and everyone for listening.
Thank you, Tara.